tbuckley/cabot-search huggingface dataset:
Prior authorizations for oral anticancer drugs and delayed prescription fills.
Authors: Michael Anne Kyle, Nancy Lynn Keating
Journal: Journal of Clinical Oncology (2023)

1504 Background: Oral anticancer drugs have proliferated in recent decades. These drugs are increasingly approved based on provisional data via the FDA’s accelerated approval pathway and have high prices, motivating payers to closely monitor how they are used. We assessed use of prior authorization (PA) of oral cancer drugs for Medicare Part D beneficiaries and assessed the impact of PA on delays in prescription fills. Methods: Using Medicare Part D formulary and claims data from 2010-2019, we described trends in Part D plans’ use of PA for oral oncology drugs, identified using the Oncology Care Model drug list (excluding hormonal therapies). We then examined changes in access to imatinib after the introduction of a new PA. We focused on imatinib because it is a highly effective first-in-class drug with a generic entrant in 2016. We compared Part D beneficiaries continuously enrolled in a plan with a policy change (new PA introduced) or a control plan (no change) in the 120 days before and after the policy change or equivalent date (control) and had at least three 30-day imatinib fills in the pre period. This restriction aimed to identify individuals filling regularly and plausibly expected to continue the drug. For each index fill in the post period, we calculated predicted fill (date of previous fill + days supply received). Our outcome variable was the difference (in days) between predicted and observed index fill date, censored at 120 days for post-period observations without an observed fill. We used an event study to model predicted vs. actual time to first fill following a policy change (new PA) relative to the controls (no change), adjusting for patient age, sex, low-income subsidy, average number of days between pre-period fills, year of fill, and plan type (standalone or Medicare Advantage). Results: The proportion of oral anticancer drugs requiring a PA increased from 52.8 to 96.3% from 2010 to 2019. For imatinib, PA increased from 65% to 89% from 2010-16, the year generic imatinib entered. PA for generic imatinib was 95% on market entry. In the imatinib event study sample, there were 1,354 index fills for patients. Unadjusted mean delay in index fill was 40 days for new PA and 15 days for controls; median difference was 4 and 3 days, respectively. Discontinuation was comparable: 9.3% (new PA) vs. 9.5% (control). The adjusted difference between predicted and actual fills for new PA was 20.3 days (95% CI 6.5-34.2, p&lt;0.004). Conclusions: Use of PA for oral oncology drugs has increased substantially over 10 years. In the setting of high prices and provisional outcomes data, PA may be appropriate. However, PA may delay fills, even for high-value drugs like imatinib. Oral anticancer drug adherence is an NCI priority; further study is warranted to identify opportunities to reduce administrative burden of PA and lessen barriers in access to effective medications.
Difference in presentation of pediatric and adult ependymoma: An NCDB analysis.
Authors: Jaylin Tuman, Quinton Anderson, Beau Hsia, Xinxin Wu, Peter T. Silberstein
Journal: Journal of Clinical Oncology (2023)

e14055 Background: Ependymomas originate from ependymal cells and account for 6.2% of primary brain tumors in the pediatric population. Adult and pediatric ependymomas are identical in histology, but present in different sites, with intracranial ependymomas seen in children and spinal ependymomas more frequent in adults. The unique presentation of ependymoma in children warrants exploration separate from adults; however, there is currently limited data providing a baseline understanding of pediatric ependymoma and those that it impacts. The National Cancer Database (NCDB) was analyzed to identify common presentations and demographic characteristics of ependymoma in children. Methods: Patients aged 18 and younger with a diagnosis of Ependymoma (ICD 9391-9394) were identified utilizing the National Cancer Database (NCDB) from 2004 – 2020 for a retrospective cohort analysis (N = 2,098). Demographic factors such as age, sex, race, ethnicity, primary site, insurance status, and surgical procedure were analyzed by descriptive statistics. Additionally, identical NCDB data was identified for patients over 18 years old for use as a comparison factor (N = 8,227). Results: A total of 2,098 pediatric patients were identified with an average age of diagnosis of 7.0 years (SD = 5.609, range = ( &lt; 1) - 18 years) with a higher percentage being male (55.9%) than female (44.1%). The vast majority of cases of pediatric ependymoma originate in the brain (91.2%), followed by occurrences on the spinal cord and cranial nerves (8.8%). This differs from ependymoma in adults where only 44.8% of cases occur in the brain and 55.2% occur in the spinal cord. Of the 2,098 pediatric patients identified, they were histologically identified as either Ependymoma, NOS (51.5%), or Anaplastic Ependymoma (47.5%). Comparatively, Anaplastic Ependymoma makes up only 9.7% of ependymomas in adult populations. Additionally, the majority of patients were Non-Hispanic (76.3%) and white (76.9%). Most patients were privately insured (58.0%) followed by those insured by Medicaid (33.1%). Pediatric ependymoma is primarily treated with surgical resection (95.7%). Conclusions: Compared to adult occurrences, pediatric cases of ependymoma are not only unique in the site that they affect but also in histology, with a higher proportion of anaplastic ependymoma. This NCDB analysis is the first to specifically analyze pediatric ependymoma and fills a gap in our understanding of how this cancer presents in children. The majority of ependymoma patients are non-Hispanic and White with a primary site occurring in the brain rather than in the spinal cord, consistent with literature. These findings emphasize the importance of a deeper understanding of the nature of this disorder. Future research should further explore the impact of demographic and socioeconomic factors on the treatments utilized, and overall survival of pediatric patients with ependymoma.
Impact of use of CDK4/6i and neratinib among patients with HER2 +ve MBC: Results from a real world dataset.
Authors: Shaheenah S. Dawood, Kaylen Brzozowski
Journal: Journal of Clinical Oncology (2023)

e13046 Background: The introduction of anti-HER2 therapy has improved the prognostic outcome of pts with HER2+ve MBC. A phase II trial revealed that among pts with HR+ve/HER2+ve MBC the use of CDK4/6i with anti-HER2 and endocrine therapy was associated with a survival advantage compared to anti-HER2 therapy and chemotherapy. A phase III trial showed that neratinib + capecitabine improved OS compared to lapatinib and capecitabine. With a plethora of new and efficacious anti-HER2 therapy now available the true clinical utility of CDK4/6i and neratinib are undetermined. The objective of this retrospective analysis was to look at the prognostic outcome associated with use of CDK4/6i and neratinib among pts with HER2+ve MBC in the real-world setting. Methods: We utilized a federated network of de-identified health data representing approximately 107 million pt lives available through the TriNetX Research Network. We identified pts with 6511pts with HER2+ve MBC diagnosed since 2015 who were treated with ant-HER2 therapy including trastuzumab, pertuzumab, neratinib, lapatinib, TDM-1 and margetuximab. OS was computed using the Kaplan Meier product limit method. HR+ve status was defined by treatment with endocrine therapy after metastasis, and triple negative (TNBC) status was identified if they did not receive anti-HER2 therapy or endocrine therapy. Results: Mean age was 57.0 yrs. 3679(57.2%) and 2832(42.8%) pts had HR+ve and HR-ve disease, respectively. 2-year OS among pts diagnosed prior to 2015 and during or after 2015 was 79.7% and 82.8%, respectively (p=0.0041). 2-year OS among pts with HR+ve and HR-ve MBC was 87.0% and 75.4%, respectively (p&lt;0.0001). Among pts with HR+ve MBC, 592(16.1%) received a CDK4/6i. Median time to use of CDK4/6i was 4.7m. 2-year OS among pts who did and did not receive a CDK4/6i was 85.1% and 87.5%, respectively (p=0.1844). Median OS among pts who received CDK4/6i within the first year of MBC diagnosis compared to those who received it after the first year of diagnosis was 71.0m and 69.4m, respectively (p=0.0679). No difference in OS was observed among pts with HR+ve disease who had brain mets who did and did not receive CDK4/6i(49.5m vs 54.5m p=0.7335). 327(5.0%) pts received neratinib, of whom 63.9% had HR+ve MBC. 2-year OS among pts who did and did not receive neratinib was 85.1% and 82.6%, respectively(p=0.2366). No difference in 2-year OS was observed among pts who did and did not receive neratinib stratified by HR status and presence of brain metastasis. Conclusions: OS among pts with HER2+ve MBC has significantly improved over time. The use of CDK4/6i among pts with HR+ve/HER2+ve MBC and use of neratinib among pts with HER2+ve MBC did not impact OS.
Carboplatin beyond 4 cycles during therapy with carboplatin, pemetrexed, and pembrolizumab for advanced non-small cell lung cancer (NSCLC).
Authors: Yaser Ahmad, Dung-Tsa Chen, Jhanelle Elaine Gray, Tawee Tanvetyanon
Journal: Journal of Clinical Oncology (2023)

e13509 Background: Since the publication of KEYNOTE-189 study , carboplatin/pemetrexed/pembrolizumab (carbo/pem/pembro) has become a common frontline regimen for advanced non-small cell lung cancer (NSCLC). In KEYNOTE-189, carboplatin was administered for a maximum of 4 cycles. To date, the number of carboplatin cycles administered in the real-world setting remains unclear. We analyzed factors predicting the receipt of carboplatin beyond 4 cycles (CB4). Methods: We interrogated a population-based, real-world database by Flatiron for NSCLC patients with no actionable EGFR/ALK who received carbo/pem/pembro from March to July 2019 (pre-pandemic period) and from March to July 2020 (pandemic period). Patients were included if they completed the regimen as shown by transitioning to maintenance pem, pembro, or pem/pembro. Primary endpoint was CB4. Secondary endpoint was overall survival. Multivariable logistic regression analyses were performed to identify independent predictors of receiving CB4. Results: Among 2090 patients treated during the study period, 966 patients (46%) started on carbo/pem/pembro and subsequently proceeded to maintenance therapy. Among them, 134 patients (14%) received CB4. Multivariable analysis revealed the following statistically significant predictors of receiving CB4, along with respective odds ratios (95% CI) and p-values: Non-white race 1.67 (1.09-2.57) (p=0.017), ECOG ≥1 1.66 (1.07-2.59) (p= 0.024), pandemic year 2020 1.68 (1.11- 2.52) (p=0.013), and ever-smoking status 0.51 (0.30-0.87) (p=0.013). Survival analysis is ongoing. Conclusions: A significant number of patients received CB4. Since this practice is not considered a standard practice, the benefits and risks of CB4 is unknown. Predictors of receiving CB4 included year of treatment, race, ECOG, and smoking status. Further investigation is needed to understand patient-physician decision making process with regards to the length of carboplatin administration. [Table: see text]
Cancer co-rounds: A novel inpatient multidisciplinary oncology rounding model.
Authors: Lisa Ni, Jennifer Viner, Christina Phuong, Siyuan John Liu, Emily Yee, Mary Petrofsky, Daniel H. Kwon, Mariza Daras, Lauren Boreta, Sam Brondfield
Journal: Journal of Clinical Oncology (2023)

e13526 Background: Although tumor boards are well-established for coordinating care of patients (pts) with cancer in the outpatient setting, few studies have evaluated interventions for improving consultative care coordination for hospitalized pts, where coordination can be particularly complex. This study evaluated the hypothesis that implementation of an inpatient co-rounding model of care including medical-, neuro-, and radiation-oncology consult teams would improve the alignment of recommendations from these oncologic services, as perceived by primary teams. Methods: A co-rounding model was implemented in September 2021 for hospitalized pts with cancer at a tertiary medical center. The oncologic consulting services met virtually twice weekly to discuss pt care. Providers from the most common primary services for pts with cancer, internal medicine (IM) and neurosurgery (NSGY), were surveyed via institutional email listservs. The survey included Likert-type questions about the alignment of recommendations across the oncologic services and open-ended questions asking for feedback on collaboration among these services. Pre-intervention surveys were distributed, and post-intervention surveys were distributed 9 months later. Thematic analysis was performed on the pre-intervention free-text responses; post-intervention free-text responses were not analyzed due to limited number. Wilcoxon rank-sum tests were used to compare responses pre- and post-intervention. Results: At each session, a median of 6 providers attended (range, 4-8 providers), and a median of 6 pts were discussed (range, 4-8 pts). Of the 331 providers surveyed, there were 119 (36%) respondents pre-intervention and 34 (10%) respondents post-intervention. The 132 unique respondents comprised 68 (52%) IM attending physicians, 48 (36%) IM resident physicians, 6 (5%) NSGY advanced practice providers, 6 (5%) NSGY attendings, and 4 (3%) NSGY residents. There were 35 total free-text responses (29 pre-intervention and 6 post-intervention). Prior to implementation, common suggested areas for improvement included: coordination between inpatient and outpatient oncologic providers (N=7), communication among inpatient oncologic services (N=6), timeliness of response to consults (N=5), and documentation of recommendations (N=4). Post-intervention, respondents were significantly more likely to perceive alignment in oncologic consultant recommendations (67% strongly agree) compared to pre-intervention (23% strongly agree, p&lt;0.01). Conclusions: A novel inpatient co-rounding model was successfully implemented between medical-, neuro-, and radiation-oncology. Primary teams perceived greater alignment in recommendations among these consulting services after implementation. Future directions include continued improvement upon the co-rounding model, and evaluation of the impact of this model on patient outcomes.
Overcoming barriers to adoption of precision medicine in community oncology centers in the rural southeastern United States using novel informatics tools and academic collaborations.
Authors: Bennett Adam Caughey, Anivarya Kumar, Jennifer R. Owen, Nicholette Sloat, Elizabeth Maynard, Vanessa Hill, Christopher Hubbard, Benjamin Neely, Matthew Stuart McKinney, Linda Sutton, Shannon J. McCall, Michael Datto, John H. Strickler, Michelle Green
Journal: Journal of Clinical Oncology (2023)

e13514 Background: Comprehensive genomic profiling (CGP) is an important tool to identify actionable biomarkers and guide cancer therapy. However, patient (pt) race, socioeconomic status, and clinical setting are associated with lower access to CGP, targeted therapies, and clinical trials. To address this, we expanded a novel framework for genomic data management and clinical decision support developed at a large academic medical center to a network of affiliated community cancer centers located in rural, traditionally underserved communities. Methods: The Duke Precision Cancer Medicine Initiative (PCMI) developed a centralized database to aggregate and normalize CGP results. This database enables CGP review by a multi-disciplinary Molecular Tumor Board (MTB). PCMI established a protocol that allows the MTB to review CGP results and relevant clinical data for consented patients. This protocol opened enrollment at four DCN-affiliated cancer centers in rural North Carolina. Clinical recommendations are captured in a standard note and returned to DCN providers following each review. Our protocol also includes an anonymous survey sent to oncology providers asking about barriers to access and utilization of CGP. Results: Between Jan 2022 and Jan 2023, 62 pts were enrolled and had CGP results reviewed by the MTB; 13 pts (21.0%) were Native American and 20 (32.3%) were Black. 61 actionable genomic alterations were identified from 38 pts, including 16 (25.6%) that molecularly matched clinical trial inclusion criteria. Most DCN providers reported being comfortable ordering (14/20) CGP though fewer expressed comfort with interpretation (9/20) CGP; provider-reported barriers included cost/insurance for targeted therapies (12/20) and distance to clinical trials (14/20). Conclusions: Successful academic-community partnerships to expand access to CGP, clinical trials, and targeted therapies are feasible when supported by fit-for-purpose informatics tools and scalable workflows. Additional work is required to develop comprehensive solutions that ensure equal access to CGP and precision medicine for all patients. [Table: see text]
Efficacy of function-enhanced, re-activatable, dual-specific CAR T cells pre-loaded with oncolytic virus for immunotherapy of high-grade glioma.
Authors: Mason Webb, Jason Tonne, Jill Thompson, Jose Pulido, Matthew C. Coffey, Houra Loghmani, Kevin Joseph Harrington, Hardev S. Pandha, Alan Melcher, Rosa Maria Diaz, Ian F. Parney, Richard Vile
Journal: Journal of Clinical Oncology (2023)

2062 Background: While cancer therapeutics have made tremendous progress within the past several decades, this benefit has not been seen in many primary cancers of the brain. Particularly confounding have been high-grade gliomas (HGG), which retain a dismal prognosis. Currently, novel therapies are being explored to rise to this unmet, critical need. One such therapy are CAR T cells, immune cells which have been engineered to target malignancy-specific antigens. Unfortunately, the efficacy of CAR T cell therapies against solid tumors is significantly limited, in large part due to impaired expansion/persistence in the immune suppressive tumor microenvironment (TME). Here we show that in vivo reactivation of CAR T cells through their native T Cell Receptor (TCR) by an oncolytic virus (OV) has therapeutic benefit in HGG. Methods: An EGFRvIII third-generation MSGV1 retroviral CAR construct containing the CD28, 4-1BB, and CD3z moieties, in tandem with the scFv derived from the human monoclonal antibody 139 and the marker Thy1.1 (38) was used to generate our CAR T cells. C57Bl/6 mice were used for in vivo experiments and both B16- and CT2A-EGFRvIII murine glioma cell lines were injected in the brain to model HGG. OVs and CAR T cells were given systemically by tail vein. OVs used include reovirus, vesicular stomatitis virus, and adenovirus. Results: By using OV in combination with EGFRvIII CAR T cells, we were able to generate a CD8 CAR population with TCR specificity for both the EGFRvIII and OV epitopes. These dual-specific (DS) CAR T expressed a memory phenotype and persisted for much longer than conventional CAR T cells. Further, we showed that these DS CAR T cells are more cytotoxic and can respond more rapidly than their conventional counterparts. We created a novel delivery mechanism for this combination OV + CAR T therapy using virus-loaded CAR T cells to bypass initial antiviral clearance from the immune system. Treatment with these OV-loaded CAR T cells lead to significant benefit in mice with HGG tumors which could be further enhanced by a systemic boost with OV, which rapidly re-activated DS CAR T cells against tumor and resulted in long-term cures of greater than 80% of treated animals. Conclusions: These promising results show that DS CAR T cells can overcome the critical therapeutic challenge of CAR T as a treatment for solid tumors. Given these promising results, we will go on to develop a clinical trial in which CAR T cells will be pre-loaded with OV and administered intravenously to patients with HGG, followed by systemic boosting with virus to re-activate DS CAR T cells against their tumor.
Telemedicine services in community oncology practices.
Authors: Kah Poh Loh, Ying Wang, Chandylen L. Nightingale, Susan K. Parsons, Christa M. Braun-Inglis, Umang Gada, Alexander Montes, Eva Culakova, Allison Magnuson, Sule Yilmaz, Sarah Strause, Charles Stewart Kamen, Karen Michelle Mustian, Gary R. Morrow, Supriya Gupta Mohile
Journal: Journal of Clinical Oncology (2023)

e13678 Background: Telemedicine services have grown tremendously due to the COVID-19 pandemic. We described the use of telemedicine for research purposes at community oncology practices. Methods: We utilized results from the National Cancer Institute Community Oncology Research Program 2017 and 2022 Landscape Surveys, which were designed to understand cancer delivery research capacity in community oncology practices. We used multivariable logistic regression to examine factors associated use of telemedicine for research purpose in 2022, adjusting for region, practice ownership type, and number of oncology providers. Results: Information was available from 504 and 685 discrete practices in 2017 and 2022, respectively. These represent 210 and 259 practice groups; practice groups serving only pediatric patients were excluded. Mean numbers of oncology providers at the practice group level were 18 (IQR 5-21) and 20 (IQR 7-22) in 2017 and 2022, respectively. Over 90% of practice groups reported having outpatient electronic health records and patient portal in both years. In 2022, IT service was available onsite in 71%. In 2017, 31% of practice groups utilized telemedicine for delivery of cancer care and 15% can utilize telemedicine for research purposes. In 2022, telemedicine was used for research purposes in 73% of practice groups. Specifically, telemedicine was used for collection of patient-reported outcomes (54%), delivery of health care interventions (47%), consent (39%), conduct of qualitative interviews (32%), delivery of behavioral interventions (30%), collection of biometric data (e.g., weight, blood pressure) (14%), and collection of neurocognitive testing data (12%). One-third of all practice groups (35%) did not have internet-abled devices available for patients, 53% had them onsite, and 2% had them on site and for patients to take home. On multivariable analysis, a greater number of oncology providers was associated with greater use of telemedicine for research purposes (every 10-unit increase, AOR 1.31, 95% CI 1.04-1.64). Conclusions: From 2017 to 2022, there has been an increased use of telemedicine for research purposes, though its use varies across practices. Bigger practice groups were more likely to use telemedicine for research purpose. Cancer care delivery research that incorporates telemedicine should consider implementing site-specific and standardized resources. [Table: see text]